Hyperthermic intrathoracic chemotherapy modulates the immune microenvironment of pleural mesothelioma and improves the impact of dual immune checkpoint inhibition.

Details

Serval ID
serval:BIB_0EE76525B2B6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hyperthermic intrathoracic chemotherapy modulates the immune microenvironment of pleural mesothelioma and improves the impact of dual immune checkpoint inhibition.
Journal
Cancer immunology research
Author(s)
Hao Y., Gkasti A., Managh A.J., Dagher J., Sifis A., Tiron L., Chriqui L.E., Marie D.N., De Souza Silva O., Christodoulou M., Peters S., Joyce J.A., Krueger T., Gonzalez M., Abdelnour-Berchtold E., Sempoux C., Clerc D., Teixeira-Farinha H., Hübner M., Meylan E., Dyson P.J., Cavin S., Perentes J.Y.
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Pleural mesothelioma (PM) is a fatal disease with limited treatment options. Recently, PM management has improved with the development of immune checkpoint inhibitors (ICIs). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. Here, we evaluated the effect of Hyperthermic IntraThOracic Chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine PM model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of PM by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.
Pubmed
Create date
29/11/2024 9:19
Last modification date
30/11/2024 7:08
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